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The year 2003 marks the 50th anniversary of the original demonstration by Edler and Hertz (1)of the feasibility of recording cardiac structure and function using pulsed reflected ultrasound. From this unheralded beginning, echocardiography has grown to become the most widely used cardiac imaging technique in the world with over 20 million studies per year currently performed in the U.S. alone. The growth in echocardiography on both the clinical and research fronts has been exponential. In the last year alone, one can identify more papers using the search term “echocardiography” than in the first 25 years after Elder's initial description combined.

Progress in echocardiography has come largely through: 1) the introduction and validation of new technology, 2) refinement or extension of existing diagnostic methods, and 3) application of new and established methods to areas of current clinical focus. This review examines the advances in each of these areas during the past year. Because of the enormous number of publications dealing with echocardiography, it is impossible to be encyclopedic, but an attempt is made to highlight important areas, to place recent advances in some perspective, and to indicate the potential and limitations of these methods.

Validation of new technology

Although the fundamental echocardiographic techniques—M-mode and two-dimensional imaging, spectral and color flow Doppler, and their combinations—for transesophageal and intravascular diagnosis have been established for many years, relatively new modifications of these technologies have recently been described or are undergoing continued clinical evaluation. These new approaches include: 1) tissue Doppler imaging (TDI), 2) strain rate and strain analysis, and 3) “real-time” three-dimensional (RT3D) imaging.

DTI

Doppler tissue imaging uses the pulsed Doppler technique (modified to record low velocity, high amplitude signals from tissue) to record the velocity and timing of myocardial motion. Because Doppler velocities are angle-dependent, most studies report velocities from myocardium moving directly toward or away from the transducer (e.g., radial velocities from the parasternal window or longitudinal velocities from any point in the left ventricle [LV] from the apical window). Longitudinal velocities are most commonly reported and may be described for individual segments (e.g., motion of the annulus toward the apex) or as an average of multiple segment velocities. Peak myocardial velocities during systole (Sm) and during diastolic rapid filling (Em) or following atrial contraction (Am) have been reported to be useful for quantifying global and regional myocardial systolic and diastolic LV function (2–4)and to correlate with prognosis in patients with a variety of cardiovascular diseases (5). Recent studies have also reported that decreased velocities in experimental models and patients with hypertrophic cardiomyopathy mutations but without hypertrophy are predictive of the development of the hypertrophic cardiomyopathy phenotype (6–8). Reduced myocardial function by TDI has also been demonstrated before the development of hypertrophy in Fabry disease patients with normal ejection fractions (9).

Although the Sm correlates reasonably well with measures of global LV function, it appears limited by both preload and afterload dependence (10). Recent reports suggest that myocardial acceleration during isovolumic contraction acceleration (IVA) (calculated as the difference between baseline and peak velocity during isovolumic contraction divided by the time interval) is a robust measure of both right ventricle and LV contractile function that is unaffected by large changes in preload and afterload (10,11). Myocardial acceleration during isovolumic contraction was also able to describe the force-frequency relationship (changes in contractility with changing heart rate) (10); IVA correlated closely with dp/dtmaxas heart rate increased from 120 to 160 beats/min (r2= 0.92). However, over the same range, there was no change in peak elastance (Emax). Thus, while the identification of an ideal measure of LV contractile function independent of preload and afterload has been elusive, these data raise the possibility that IVA may be such an index that can be obtained noninvasively. Additional studies will be necessary to validate these results in the clinical environment in normal and diseased ventricles.

Several recent experimental and clinical studies have also expanded our understanding of the role of TDI in the assessment of diastolic function. Measurement of early (Em) and late (Am) diastolic myocardial velocities along the long axis of the LV at the level of the mitral annulus have been shown to be useful for determining LV relaxation and filling pressure; however, the peak myocardial velocity (Em) is load-dependent in normal subjects. In an experimental study, Hasegawa and colleagues (12)showed that the normal LV expands symmetrically during rapid early filling and that peak longitudinal expansion, like radial expansion, occurs coincident with the peak E wave and cross-over of the left atrium-LV pressure gradient (12). However, after pacing-induced heart failure, this synchrony of relaxation was altered, and longitudinal expansion was delayed, occurring after the crossover of left atrium-LV pressure, and was relatively independent of left atrium pressure because Em occurred after the left atrium-LV gradient had reversed. Although the authors observed a very good correlation between Em and tau (r2= 0.85), the best correlation was between the time from the peak of the E-wave (peak transmitral flow velocity) to the peak of the Em-wave (TEm-Ems) and tau (r2= 0.97). Similarly, in a combined experimental and clinical study, it was reported that IVC occlusion resulted in a significant decrease in Em before, but not after, circumflex ligation, whereas its effect on the time interval (TEm-E) was minimal under both circumstances (13), supporting the relative preload independence of the time interval. Clinical studies confirmed the relationship of TEm-Eto tau (tau = 32 + 0.7 TEm-E, r = 0.83), its ability to distinguish normal from pseudonormal inflow patterns, and its potential use in predicting pulmonary capillary wedge pressure. Unfortunately, the actual time intervals measured were very small (<40 ms), several measurements are required, each with its own inherent errors, and subjects with mitral valve disease were excluded, so that the ultimately clinical utility remains to be determined.

Tissue Doppler has also been proposed as an attractive technique for quantifying segmental function during stress echoes because TDI: 1) compares well with reference methods such as sonomicrometry, 2) permits sensitive assessment of segmental myocardial function, and 3) is sensitive to inotropic stimulation and ischemic challenge (14). In diabetic patients with normal ejection fractions studied before and during dobutamine stress echocardiography (DSE), Fang et al. (15)reported that at baseline both Sm and Em were reduced compared with controls. However, with inotropic stimulation, both indexes augmented normally, suggesting that TDI may detect microvascular or tissue structural changes before the development of abnormalities in the standard measures of systolic function or loss of inotropic response (15).

Strain and strain rate imaging (SRI)

Strain rate imaging is a recently described modification of TDI that provides a quantitative measure of regional myocardial function (16). Strain rate is defined as the difference in myocardial velocities (as defined by TDI) between two axial points (usually separated by 1 cm) along the path of the echocardiographic beam per unit time (17). Strain is the integral of strain rate over time, and these measures represent the instantaneous and total deformation of the myocardium within the sampled region. Strain rate and strain appear to be relatively load-independent quantitative measures of function, and can potentially be determined for different layers of the myocardium (18). Although derived from tissue velocities, these measures are relatively unaffected by translation and tethering and, thus, have been suggested to be more specific than TDI alone.

Strain rate and strain have been proposed as useful quantitative measures of myocardial function in ischemia, particularly during stress echocardiography. In a study performed during DSE, the ratio of post-systolic to peak strain was demonstrated to yield the best sensitivity and specificity for detecting ischemic segments. Unfortunately, the incremental increase in sensitivity and specificity over visual assessment of wall motion was small (81% to 82% and 86% to 89%, respectively) (19). The ability of strain rate and strain to differentiate nontransmural from transmural infarction during dobutamine stress was also demonstrated in an experimental study (20).

Strain rate and strain have also been reported to detect changes in baseline function in a variety of conditions before abnormalities in conventional measure of performance such as the ejection fraction. In patients with amyloidosis TDI, strain rate and strain were compared for the detection of early dysfunction before the development of congestive heart failure. Mean strain rate and strain, but not TDI, were both significantly different in amyloid patients with and without congestive heart failure from the controls (21). Strain and strain rate measurements also demonstrated improvement in function in patients with Fabry's disease after 12 months of enzyme replacement therapy (22). In patients with hypertension and preserved systolic function, it was demonstrated that strain rate and strain were lower than in controls (23). These studies support the concept that strain rate and strain may be abnormal even when ejection fraction and fractional shortening are normal and, hence, are earlier markers of myocardial dysfunction than conventional measures. At present, however, these measurements of strain rate and strain are angle-dependent, the data can be quite noisy, and significant expertise is required to identify appropriate recordings for analysis.

Three-dimensional echocardiography

The evolution of parallel processing techniques that permit multiple, b-mode data lines to be acquired for each transmitted pulse and matrix array transducers that allow the beam to be flexibly directed within a three-dimensional volume have permitted the direct acquisition of a true RT3D data set. The advantages of RT3D imaging are that acquisition is faster, data is acquired in a spatially correct orientation without the need for electrocardiogram or respiratory gating, and the images are immediately available for analysis. In addition, orthogonal planes can be recorded simultaneously with full two-dimensional image resolution (24). Validation studies have confirmed that, like earlier three-dimensional reconstruction approaches, RT3D is superior to standard two-dimensional methods in the determination of LV volume, mass, perfusion territory defined by myocardial contrast echocardiography (MCE), and right ventricle volumes (25–27). Unfortunately, despite parallel processing, the line density in the three-dimensional volume is less than in a two-dimensional image requiring more interpolation between data points; the beam may not be optimally aligned to record all structures within the imaged volume reducing image quality; and the “frame rate” is slower than conventional two-dimensional imaging. Despite these limitations, the more rapid acquisition time and immediacy of data availability will undoubtedly make RT3D imaging the method of choice for most clinical applications.

The task of simplifying acquisition and segmentation for ventricular and atrial volume and LV mass measurement remains essential for routine clinical application of three-dimensional echocardiography. Several freehand three-dimensional echocardiography studies were reported: Dorosz et al. (34)described a three-dimensional-guided, two-dimensional imaging method using a freehand transducer to improve the accuracy of imaging plane selection for measuring right ventricle volumes. Three-dimensional freehand scanning for LV volume and ejection fraction calculations were also validated by Mannaerts et al. (35)with magnetic resonance imaging and Kawai et al. (36)with gated scintigraphy. Wong et al. (37)report on a novel catalog-based method for quantifying LV volume from a limited number of traced points. Handke et al. (38)also studied aortic valve geometry and motion using a new, high-frame rate system for three-dimensional echocardiography based on direct acquisition of the radiofrequency signal. Thus, the potential applications for three-dimensional echocardiography imaging continue to increase. Improvements in transducer technology and processing speed for RT3D image acquisition in conjunction with real-time volume rendering should make it possible to integrate three-dimensional imaging into the routine clinical examination of selected patients.

Refinements and advances in existing technologies

Tissue characterization

Ultrasonic tissue characterization is based on quantitation of the backscattered signals arising from within the myocardium. Alteration in tissue properties due to edema, fibrosis, and calcification have been demonstrated in experimental and human studies to alter ultrasonic backscatter (39). A number of measures of backscatter have been reported including: 1) the mean integrate backscatter (IB) (backscatter averaged over the cardiac cycle) and often expressed as the ratio of IB in the region of interest to some reference area within the image (e.g., the blood pool) to correct for attenuation, or 2) cyclic variation in integrated backscatter CVIB (measured as the difference between the nadir and peak of the IB signal during the cardiac cycle). Cyclic variation in IB has been suggested to be more sensitive than standard measures of cardiac function in certain settings and does not require calibration for attenuative losses. Integrated backscatter, in contrast, has been most closely correlated with tissue collagen content. Changes in IB have been reported to occur in a variety of pathologies including ischemia and infarction, cardiomyopathy, atherosclerosis, and transplant rejection. In the past year, IB has been reported to provide unique information in a variety of pathologies including Duchenne muscular dystrophy (40), essential hypertension, acute myocardial infarction with spontaneous reperfusion, and congenital aortic stenosis (41). In children with Duchenne muscular dystrophy, IB has been reported to identify early changes in myocardial structure (cyclic variation in IB decreased and mean calibrated IB increased) before the development of overt cardiomyopathy or expected collagen increase (40). Cyclic variation in IB has also been shown to correlate with LV mass in patients with essential hypertension but to predict changes in function before changes in fractional shortening (42). Changes similar to those seen with hypertrophy were reported in diabetics that were independent and incremental to the effects of LV hypertrophy (15). In patients with acute anterior wall infarcts, phase-corrected cyclic variation in IB was found to predict spontaneous reperfusion with a sensitivity of 96% and specificity of 90% (43). While IB can often differentiate between normal and disease states, absolute values for IB are not disease-specific. In addition, because IB is angle-dependent, only signals from structures that are perpendicular to the path of the ultrasound beam are usually analyzed.

MCE

Recent advances in MCE have focused on the development of new, more stable contrast agents with shell properties that permit interaction with the endothelium, the use of targeted bubble destruction for the local delivery of adenoviral or plasmid DNA (44), and the clinical validation of MCE after intravenous contrast injection to reliably assess myocardial perfusion and predict recovery of function after mechanical restoration of coronary flow.

Ultrasound microbubbles targeted to the leukocyte adhesion molecule ICAM-1 by conjugation with anti-ICAM-1 antibody have been shown to preferentially bind to inflammatory, cultured human endothelial cells. Microbubble adhesion has been shown to relate to surface antibody concentration and shear rates (45). More recently, targeted contrast uptake was shown to increase in an in vivo model of transplant rejection (46). Another agent that consists of a perfluorobutane bubble stabilized by a phospholipid monolayer was shown in experimental studies to accumulate in the myocardium with the result that 15 min after injection the concentration in the myocardium was 2.1 times that in the LV cavity. In addition, during coronary reperfusion the contrast intensity in the risk area was paradoxically increased, creating a “bright spot” despite reduced perfusion (47). If validated in clinical studies, the potential of these specially designed bubbles to enhance diagnosis and augment drug and gene delivery is enormous.

Clinical studies have focused on the ability of intravenous MCE to detect myocardial ischemia and predict recovery of function after interventional procedures. In a multicenter trial, MCE was compared with single photon emission computed tomography during dipyridamole stress testing for the detection of ischemia. Good correlation was found, and after correcting the single photon emission computed tomography data for angiographic lesions, examples were presented in which MCE was more reliable. This study was limited by low enrollment, with only 43 patients available for study and catheterization in only 15 (48). The ability of MCE to predict recovery of function after coronary intervention was examined in several studies. In patients with acute myocardial infarction treated by stenting, MCE predicted recovery with a sensitivity of 88% and specificity of 74% (49). Myocardial contrast echocardiography was also compared with DSE and rest-redistribution TI 201 tomography for the prediction of recovery of function after coronary artery bypass grafting. Studies performed before coronary artery bypass grafting were compared with recovery of function three to four months after surgery. The product of peak myocardial contrast intensity × β was the best parameter for predicting recovery of function, had a similar sensitivity to, but higher specificity than, TI 201, and improved the accuracy of DSE in predicting recovery of function. However, qualitative MCE was feasible in only 80% of segments, whereas quantitative MCE was feasible in only 74%, highlighting a potential limitation of MCE (50). Myocardial contrast echocardiography was also reported to be superior to ST-segment resolution on the 180 min electrocardiogram, corrected Thrombolysis in Myocardial Infarction frame count, and myocardial blush grade in predicting wall motion score index within the risk area at four weeks (51). These clinical studies, although largely confirmatory and limited by small numbers, lend continued support to the potential application of MCE in patients with ischemic heart disease.

Stress echocardiography

Despite the proven accuracy of DSE, its sensitivity and specificity are imperfect (particularly in single-vessel disease) and may be affected by difficulties in appreciating subtle wall motion abnormalities at peak stress in the tachycardiac, hyperdynamic LV (52). Mathias et al. (53)report that metoprolol injected (5 mg intravenous) immediately after acquisition of peak stress images raised the sensitivity of DSE, especially in patients with single-vessel coronary artery disease, without a significant loss of specificity.

Recent clinical stress echocardiography studies have primarily centered on the evaluation of prognosis in large populations with acute and chronic coronary artery disease and have confirmed that dipyridamole or DSE are effective in predicting cardiac death during long-term follow-up (54,55), that a negative test is associated with a favorable outcome (54), and that the location (anterior wall) of ischemia is predictive of increased risk of cardiac death and nonfatal myocardial infarction independent of the extent of abnormal wall motion (56). In addition, it has been demonstrated that a biphasic response (improvement at low stress followed by deterioration with increased stimulation) can be seen with exercise as well as dobutamine stress in patients early after acute myocardial infarction and is an accurate tool for detecting infarct-artery-related stenosis and predicting functional recovery (57). Interestingly, in patients with suspected coronary artery disease (based on suspected angina equivalent [dyspnea or palpitations], multiple risk factors, or the desire to exclude coronary artery disease because of occupation [total n = 1,859]) but without classic angina, exercise echocardiography added no additional prognostic information beyond that provided by a standard exercise test and resting echocardiogram (58).

Application of new and established technologies to areas of current clinical focus

Cardiac resynchronization therapy (CRT)

Recent controlled clinical trials have demonstrated both acute hemodynamic and long-term functional benefit from CRT with biventricular pacing in a subgroup of patients (comprising ∼60% to 70%) with class III/IV heart failure and left bundle branch block (59–61). Because CRT is complex and expensive, identification of patients most likely to benefit is important. Several recent studies suggest that the direct assessment of the degree and timing of dyssynchronous wall motion by a variety of echocardiography methods including M-mode echocardiography, Fourier analysis of phasic change in two-dimensional recordings (61), tissue Doppler, strain rate, and strain recordings may better identify patients more likely to benefit from CRT than the surface electrocardiogram (61–63).

Longer term results were reported by St. John Sutton and colleagues (64)who analyzed LV volumes, ejection fraction, mass, degree of mitral regurgitation, LV filling time, and performance index at baseline and after three and six months of CRT in 323 patients from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Significant reductions in LV volumes occurred at three months and continued from three to six months in the CRT group but not in controls. There was also a small, but significant, increase is ejection fraction at six months (3.6% vs. 0.4% p < 0.01). Mitral regurgitation jet area and LV mass also declined, but LV shape did not change. Changes in LV end-diastolic volume and ejection fraction from baseline to six months were significantly greater (twofold) in patients with nonischemic LV dysfunction than in patients with equivalent LV dysfunction due to ischemic heart disease. Importantly, changes in LV end-diastolic volume and ejection fraction in the CRT group were independent of B-adrenergic blockade (64).

Although global measures of LV performance clearly improve in most patients after CRT, the assessment of regional performance is more complex. In the presence of asynchrony, there is regional redistribution of myocardial fiber strain with associated changes in regional blood flow and metabolism (65). In a study by Breithardt et al. (66), early systolic septal shortening was often accompanied by lateral wall lengthening. Late activation of these stretched lateral wall segments was associated with higher peak negative strain rate and wall stress. Cardiac resynchronization therapy led to redistribution of longitudinal myocardial deformation with the majority of patients being well synchronized or “oversynchronized” (i.e., the lateral wall shortened before the septum) (66). Although in theory restoration of synchrony in myocardial strain should increase energy efficiency and result in favorable global remodeling, further studies are necessary to confirm these effects.

The presence of functional mitral regurgitation in heart failure appears to be strongly dependent on alterations in LV shape, as the tethering forces that act on the mitral leaflets are higher in dilated, more spherical ventricles (67–69). In an elegant study, it was shown that CRT caused an increase in the peak closing force as well as an increase in LV + dp/dtmaxduring isovolumic contraction (70). These changes effectively counteracted the increased tethering forces that impair mitral leaflet closure and decreased the effective regurgitant orifice area. Although the changes in functional mitral regurgitation produced by CRT in this acute study occurred in the absence of reverse remodeling, this phenomenon could further reduce functional mitral regurgitation during chronic therapy.

Coronary arteries

Recent studies support the ability of transthoracic Doppler recordings to detect restenosis in the left anterior descending coronary artery after coronary angioplasty based on a ratio of baseline to hyperemic coronary flow ≤2 (sensitivity 89%, specificity 90%) (71). When compared with abnormal wall motion by DSE for the detection of left anterior descending coronary stenoses, coronary flow velocity reserve (CFVR) ≤2 had a sensitivity of 75% and a specificity of 79% versus 78% and 89%, respectively, for DSE (72). These methods have now been extended to include the posterior descending coronary artery and applied to children with Kawasaki disease (73). In Kawasaki patients, peak and mean CFVR were lower in those with significant angiographic stenosis with a CFVR of <2.0, predicting significant coronary stenosis with a sensitivity of 89% and a specificity of 96%. In adults, recording the posterior descending artery has proven more difficult but can be improved with contrast injection (∼80%) (74). Success rates are higher with right dominant and balanced circulations, and correlations with Doppler flow wire measurements have been good (r = 0.85). Despite these promising results, noninvasive recording of coronary flow is technically demanding, and the absence of flow is difficult to interpret. The role of this technique relative to other methods for detecting ischemia remains to be defined.

Left atrium

Interest in the left atrium has been stimulated by the recent clinical focus on treatment of atrial fibrillation, the relationship of atrial fibrillation and left atrial enlargement to embolic stroke, and the value of left atrial volume (LAV) as a predictor of diastolic dysfunction.

Recent studies have examined the relationship of echocardiographically defined left atrium volume to clinical outcomes in a variety of clinical situations. In a study designed to examine whether subclinical abnormalities detected by echocardiography are predictive of first age-related cardiovascular events in an elderly population, LAV was found to be independently predictive in a multivariate model containing age, diabetes, gender, systemic hypertension, LV systolic function, LV diastolic function, and LV mass. In contrast, presenting symptoms (chest pain, dyspnea, lightheadedness, palpitations, presyncope, syncope) leading to echocardiographic referral were not independently predictive in univariate or multivariate models. Although the other components of the model have previously been shown to predict risk, the contribution of left atrium volume to risk has not been widely appreciated (75).

In a study of patients with acute myocardial infarction, the LAV index (LAV/body surface area [BSA]) was a predictor of mortality even after adjustment for conventional indexes of systolic and diastolic function (76). These observations are in agreement with prior data that LV ejection fraction is not an independent predictor of outcome in acute myocardial infarction when assessment of diastolic function is available (77,78). The additional valve of LAV/BSA to standard assessments of diastolic function is attributed to the relationship of LAV to the duration and severity of elevated LV filling pressures as opposed to Doppler indexes that are preload-dependent and reflect instantaneous change in the transmitral gradient.

Pulmonary embolism

Small series have described the prevalence, natural history, and prognostic significance of right heart thrombi in patients with pulmonary embolism. In a series of 1,113 patients from the international cooperative pulmonary embolism registry, Torbicki et al. (79)reported that 4% of patients with pulmonary embolism had right heart thrombi. This group had a shorter duration of symptoms, lower systolic blood pressure, and more frequent right ventricular hypokinesis and congestive heart failure than patients with pulmonary embolism but without right heart thrombi. The overall mortality at two weeks and three month was higher for the group with right heart thrombi (21% vs. 11% and 29% vs. 16%, respectively) with the differences in mortality in the right heart thrombi group being almost entirely in the subgroup treated with heparin despite similar clinical severity at presentation.

Valvular heart disease/hemodynamics

valvular stenosis

The stenotic valve area is usually measured at catheterization using the Gorlin formula or by echocardiography using the continuity equation. However, there are often discrepancies in these measures that are attributed to the effects of pressure recovery. Pressure recovery occurs when the streamlines of flow passing through an area of stenosis reexpand and reattach to the vessel wall with the result that kinetic energy is converted back to pressure energy (80,81). Conversely, the pressure loss distal to a stenosis is due to the turbulence that occurs when the high velocity jet encounters stagnant fluid within the aortic sinus as it seeks to expand. It is the turbulence at this boundary that dissipates energy (i.e., kinetic energy is lost as heat) and limits pressure recovery. The smaller the aorta, the less the opportunity for the development of turbulence, and, hence, the greater the pressure recovered. Therefore, the magnitude of the recovered pressure relates to ratio of effective orifice area to the ascending aortic area. Doppler measures of aortic valve area rely on the peak velocity or gradient measured across the aortic valve and reflect the true effective orifice area, while catheterization measures that use the pressure gradient after pressure recovery (the net pressure loss) will yield larger values for effective orifice area. Although the effective orifice area cath is a less accurate measure of the physiologic effective orifice area, it appears to be a better measure of outcomes because is it derived from the true energy loss to the system. Several recent studies have suggested methods for correcting the Doppler effective orifice area for the effects of pressure recovery. They propose an “energy loss coefficient” that adjusts the Doppler effective orifice area for factors that determine the energy loss across the valve in which the Doppler effective orifice area is multiplied by Aa/(Aa − EOA) = 1 + (EOA/(Aa − EOA), where Aa is the area at the sinotubular junction and EOA is effective orifice area (82). As might be expected, the greatest discrepancies occur in patients with the smallest aortas where pressure recovery is the greatest. Understanding this relationship is important, particularly in the evaluation of patients whose areas are at the border of severity grade. Whether actual correction is necessary is unclear because, although the percent difference may be significant, the absolute differences are small, particularly when viewed in the context of the standard error of these measurements (in most studies ∼0.2 cm2). However, these studies emphasize the importance of aortic dilation because, for a constant valve area, dilation of the aorta, by itself, can significantly decrease pressure recovery and, hence, independently increase the effect of a stenosis (82,83). In another study, it was shown that a measure of stroke work loss (SWL) defined as SWL = 100 · P/(ΔP + SPB) was the most clinically efficient Doppler measure (when compared with Vmax, ΔP, or aortic valve resistance) in terms of predicting symptomatic status and outcome (84). Here again, although the differences were not great, it appears that measures that emphasize the loss of energy are the most appropriate for determining clinical relevance. Importantly, these discussions reemphasize the fact that the Doppler-derived aortic valve areas are generally smaller than those reported at catheterization and may lead to misclassification of severity using current catheter-based recommendations, They also remind us that the impact of aortic stenosis on the LV is due to energy loss or wastage rather than a simple measure of gradient or area, and that the size of the aorta and the inlet geometry of the valve (85)are important determinants of energy loss independent of valve area.

Valvular regurgitation

Ischemic mitral regurgitation has been shown to be due to displacement of the papillary muscles, which increases the tension on the mitral leaflets displacing them away from the annulus and increasing the leaflet area necessary to completely occlude the annulus. This effect is augmented by annular dilation and modified by leaflet length. Because of the geometry of the chordal insertions, the maximal tension is exerted by the basal or intermediate chords, which attach to the midportion of the anterior leaflet. Recent experimental studies have suggested that transection of the central basal chords could reduce the severity of mitral regurgitation without causing prolapse. In a report by Messas et al. (86), these observations were extended to the chronic model where it was shown that cutting a minimal number of basal chords decreased regurgitation without causing prolapse or adversely effecting LV function. Using an alternative approach, Hung et al. (87)demonstrated that reversing ventricular remodeling using an externally positioned inflatable device returned the papillary muscles to a more normal position and reduced the severity of mitral regurgitation. Although performed in experimental animal models, these reports suggest that modification of mitral valve tethering may be a useful adjunct to annular plication in the treatment of ischemic mitral regurgitation.

Preoperative risk stratification

In a multicenter trial to confirm the value of dobutamine stress testing in preoperative risk stratification in patients with low gradient (≤40 mm Hg), but severe, aortic stenosis (aortic valve resistance ≤1.0 cm2), it was shown that an increase in cardiac output by ≥20% compared with baseline was associated with a marked decrease in surgical mortality (5% vs. 32%) and improved postoperative functional recovery. Predictors of long-term survival were valve replacement and preoperative contractile reserve (88). Relative aortic stenosis (an increase in valve area ≥0.3 cm2, with a final valve area >1 cm2) during dobutamine stress testing was found in only 5% of patients in this study and in contrast with earlier reports and was not associated with a good prognosis.

Miscellaneous

In a letter to the editors of the New England Journal of Medicine, Aepfelbacher, Breen and Manning (89)noted that reports on the safety of transesophageal echocardiography in more than 25,000 patients and upper gastrointestinal endoscopy in more than 500,000 patients do not list methemoglobinemia as a potential complication (89). Methemoglobinemia results from oxidation of ferrous iron (Fe 2+) to ferric iron Fe+++, which renders the hemoglobin molecule unavailable for oxygen transport and may be triggered by the topical anesthetic used in endoscopic procedures. They report two cases experienced in their laboratory in a three-month period. Methemoglobinemia was characterized by a fall in arterial oxygen saturation, unrelieved by 100% oxygen, and cyanosis. We have also noted four cases of methemoglobinemia developing during transesophageal echocardiography procedures in the last year, all requiring treatment with intravenous methylene blue (1 to 2 mg/kg given over a 5-min period). Individuals performing transesophageal echocardiographies, therefore, should be aware of this underemphasized complication.

Summary

During the past year, progress in echocardiography has been reported in many areas with new methods available to answer increasingly sophisticated clinical and research questions. As these new techniques mature, existing methods have and will continue to expand our understanding of important clinical issues and further clarify mechanisms of cardiac disease.

(2001) Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy. Circulation104:128–130.

(2002) Validation of myocardial acceleration during isovolumic contraction as a novel noninvasive index of right ventricular contractility: comparison with ventricular pressure-volume relations in an animal model. Circulation105:1693–1699.

(2003) Discrepancies between catheter and Doppler estimates of valve effective orifice area can be predicted from the pressure recovery phenomenon: practical implications with regard to quantification of aortic stenosis severity. J Am Coll Cardiol41:435–442.

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